antibioticsbooks

chapter 37 Serine Protease Inhibitors 247
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Important Facts
• Serine protease inhibitors must be given in
combination with pegylated interferon and
ribavirin. If they are not, resistance quickly
emerges to them in HCV.
• Serine protease inhibitors inhibit CYP450 3A4
and so have many drug interactions. Many of
these interactions have not yet specifically been
studied, so be wary in how you use these drugs
in patients taking other drugs metabolized
by this pathway. The website http://www.hep
-druginteractions.org is an excellent resource
for assessing drug interactions with drugs for
viral hepatitis.
• Though they are inhibitors of HCV protease
enzymes, HCV serine protease inhibitors are
not active against HIV. They do, however, interact
with many HIV medications, including HIV
protease inhibitors.
• For boceprevir, a lead-in period of four weeks
of pegylated interferon and ribavirin is given
before boceprevir is started. The purpose of
the lead-in period is to decrease the amount of
HCV so resistance is less likely to emerge during
therapy and is how boceprevir was studied.
Telaprevir does not utilize a lead-in period.
• Resistance to these agents does emerge during
therapy and seems to correlate with failure to
eradicate HCV. The genetic barrier for resistance
emergence seems low, so compliance is
important.
• Telapreveir and boceprevir are indicated to
be given with different forms of pegylated
interferon-a and their accompanying doses of